E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 19.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10009955 |
E.1.2 | Term | Colon cancer stage III |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To determine whether the Oxaliplatin dose adaptation/normalization based on the lean body mass index can prevent or reduce neurotoxicity associated with Oxaliplatin, for stage III colon cancer patients treated in adjuvant setting with simplified FOLFOX 4 regimen. |
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E.2.2 | Secondary objectives of the trial |
To determine the impact of the Oxaliplatin dose adaptation/normalization based on the lean body mass index on:
- Treatment compliance and cumulative Oxaliplatin doses that can be delivered without dose-limiting chronic neurotoxicity.
- Patients’ quality of life
- Disease-free survival and overall survival.
To describe baseline and post-treatment neurological quantitative sensory testing abnormalities in these patients.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Age: more than 18 years old up to 75 years old including. Histologically confirmed adenocarcinoma of the colon.
- Has undergone a curative resection for stage III colon cancer.
- Scheduled to receive 6 months of Oxaliplatin-based adjuvant chemotherapy at a dose of 85 mg/m² of Oxaliplatin every 2 weeks (simplified FOLFOX 4 regimen).
- The following laboratory values obtained ≤ 28 days prior to inclusion:
WBC ≥ 3000/mm3; ANC ≥1500/mm3; PLT ≥100,000/mm3; HgB ≥10.0g/dl; Total bilirubin ≤1.5 x upper normal limit (UNL); Serum creatinine ≤1.5 x UNL; Serum calcium ≤ 1.2 x UNL; Serum magnesium ≤ 1.2 x UNL.
- Central venous access line present or patient scheduled to have a central line placed prior to starting chemotherapy or the treatment protocol.
- Negative pregnancy test (serum or urine) done ≤ 7 days prior to registration, for women of childbearing potential only.
- Ability to complete questionnaire(s) by themselves or with assistance.
- ECOG Performance Status (PS) of 0, 1 for patients until 70 years old included and ECOG PS of 0 for patients between 70 to 75 years old included.
- Has provided informed written consent.
- Patient willing to provide blood sample for research purposes
- Patient affiliated to a French social security system
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E.4 | Principal exclusion criteria |
- Pregnant or breastfeeding women
- Men or women of childbearing potential who are unwilling to employ adequate contraception since this study involves agents that have known genotoxic, mutagenic and teratogenic effects
- Pre-existing peripheral neuropathy of any grade.
- Prior treatment with neurotoxic chemotherapy such as Oxaliplatin, cisplatin, taxanes, or vinca alkaloids.
- Treatment with 1) the anticonvulsants carbamazepine (e.g., Tegretol®), phenytoin (e.g., Dilantin®), valproic acid (e.g. Depakine®), gabapentin (Neurontin®); pregabalin (Lyrica®); 2) the following neurotropic agents: venlafaxine (Effexor®), desvenlafaxine (Pristiq®), milnacipran (Savella®) or duloxetine (Cymbalta®); 3) Tricyclic antidepressants (such as amitryptilline) or 4) any other agent specifically given to prevent or treat neuropathy.
- Family history of a genetic/familial neuropathy.
- Participation in another medication trial within 30 days prior to study entry
- Legal incapacity or physical, psychological social or geographical status interfering with the patient's ability to sign the informed consent or to terminate the study
- History of other solid tumor in 3 years before the inclusion, excepted of cancer in situ of the cervix and skin cancer (basal or squamous cell) treated and controlled.
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E.5 End points |
E.5.1 | Primary end point(s) |
Percentage of patients without experiencing grade ≥ 2 of neurotoxicity (paresthesia according to the NCI-CTCAE version 4.03) at any time during the first 6 cycles of adjuvant Oxaliplatin-based chemotherapy |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
last visit of the last patient |
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E.5.2 | Secondary end point(s) |
- The cumulative Oxaliplatin doses that can be delivered without reaching the dose-limiting chronic neurotoxicity (according to the NCI-CTCAE version 4.03) and the percentage of patients discontinuing Oxaliplatin-based chemotherapy due to neurotoxicity will be evaluated.
- The evolution of quality of life will be assessed with repeated measurements using the EORTC QLQ-C30 questionnaire during chemotherapy and follow-up.
- The evolution of the Oxaliplatin-induced sensory neuropathy will be assessed with repeated measurements using the EORTC QLQ-CIPN20 sensory subscale during chemotherapy.
- Time to onset of grade ≥ 2 chronic cumulative neurotoxicity (according to the NCI-CTCAE version 4.03),
- Duration of the chronic cumulative neurotoxicity (according to the NCI-CTCAE version 4.03) during and after adjuvant Oxaliplatin-based chemotherapy.
- Incidence of other adverse events as measured according to the CTCAE version 4.03.
- Disease-free survival
- Overall survival
- The five dimensions of the EQ-5D questionnaire |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
last visit of the last patient |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | No |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
Oxaliplatin with the dose calculated on lean body mass |
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E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 22 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 5 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |